Interest in global pharmacy research partnerships is growing, and many Schools and Colleges of Pharmacy are looking to expand their footprint in the global health arena. This will create opportunities for increased collaboration and synergy, but there will also be concerns for potential duplication and fragmentation. Such research partnerships also present unique opportunities for addressing unmet medication-related needs of populations around the word, especially for vulnerable populations living both in high income countries (HICs) and low- and middle-income countries (LMICs). Pharmacy leaders and researchers engaged in global health partnerships or planning to start one can draw important lessons from other global health partnerships but also by studying the historical context and evolution of global health initiatives. To be meaningful, global pharmacy research partnerships must be grounded in local contexts and be sensitive to the myriad influences and actors that may determine success of their research endeavors, including health interventions. A deliberate and thoughtful investment in mentorship and faculty development for LMIC collaborators are also essential ingredients for sustainability of global research partnerships.Cystic fibrosis (CF), a genetic disease caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, is characterized by dysfunction of the immune response in the airway epithelium that leads to prolonged infection, colonization and exacerbated inflammation. In this study, we determined the gene expression profile of airway epithelial cells knockdown for CFTR (CFTR KD) in response to bacterial and viral challenges.
In a first approach, polarized CFTR KD and their control counterpart (CFTR CTL) cells were stimulated with P. aeruginosa-derived virulence factor flagellin. Next, we developed a model of Influenza A virus (IAV) infection in CTL and CFTR KD polarized cells. mRNA was collected for transcriptome analysis.
Beside the expected pro-inflammatory response, Gene Set Enrichment Analysis highlighted key molecular pathways and players involved in IAV and anti-viral interferon signaling. Although IAV replication was similar in both cell types, multiplex gene expression analysis revealed changes of key immune genes dependent on time of infection that were found to be CFTR-dependent and/or IAV-dependent. Interferons are key signaling proteins/cytokines in the antibacterial and antiviral response. To evaluate their impact on the altered gene expression profile in CFTR responses to pathogens, we measured transcriptome changes after exposure to Type I-, Type II- and Type III-interferons.
Our findings reveal target genes in understanding the defective immune response in the CF airway epithelium in the context of viral infection. Information provided in this study would be useful to understand the dysfunctional immune response of the CF airway epithelium during infection.
Our findings reveal target genes in understanding the defective immune response in the CF airway epithelium in the context of viral infection. Information provided in this study would be useful to understand the dysfunctional immune response of the CF airway epithelium during infection.Patients with type 2 diabetes mellitus characteristically display an atherogenic lipid profile with high triglyceride concentrations, low high-density lipoprotein cholesterol (HDL-C) concentrations and low-density lipoprotein cholesterol (LDL-C) concentrations not always elevated. It is unclear if patients with diabetes who present with an acute coronary syndrome (ACS) receive different or more-potent lipid-lowering therapy (LLT).
To investigate lipid abnormalities in patients with and without type 2 diabetes hospitalised for an ACS, and use of LLT before admission and 4 months after the event.
Patients were included in the observational DYSIS II study if they were hospitalised for an ACS and had a full lipid profile.
Of 3803 patients, diabetes was documented in 1344 (54.7%). Compared to patients without diabetes, those with diabetes had a lower mean LDL-C (101.2 vs. 112.0mg/dL; 2.6 vs. 2.9mmol/L; P&lt;0.0001), with a greater proportion attaining concentrations&lt;70mg/dL (1.8mmol/L) (23.9% vs. 16.0%;There was no difference in LLT in patients with and without diabetes at 4-month follow-up, except for fibrates, which were used in 2% of patients with and 1% of patients without diabetes. Statin monotherapy of intermediate potency was the predominant treatment in both groups.Transthoracic echocardiography (TTE) and transoesophageal echocardiography (TOE) can be used to detect the presence of left atrial thrombus and left atrial spontaneous echocardiographic contrast (LASEC).
To evaluate the prognostic value of TTE and TOE in predicting stroke and all-cause death at 5-year follow-up in patients with non-valvular atrial fibrillation (NVAF).
This study included patients hospitalised with electrocardiography-diagnosed NVAF in Saint-Antoine University Hospital, Paris, between July 1998 and December 2011, who underwent TTE and TOE evaluation within 24hours of admission. https://www.selleckchem.com/products/apocynin-acetovanillone.html Cox proportional-hazards models were used to identify predictors of the composite outcome (stroke or all-cause death).
During 5 years of follow-up, stroke/death occurred in 185/903 patients (20.5%). By multivariable analysis, independent predictors of stroke/death were CHADS-VASc score (hazard ratio [HR] 1.35, 95% confidence interval [CI] 1.25-1.47; P&lt;0.001), left atrial area&gt;20 cm(HR 1.59, 95% CI 1.08-2.35; P=0.018), moderate LASEC (HR 1.72, 95% CI 1.13-2.62; P=0.012) and severe LASEC (HR 2.04, 95% CI 1.16-3.58; P=0.013). Independent protective predictors were dyslipidaemia (HR 0.60, 95% CI 0.43-0.83; P=0.002) and discharge prescription of anti-arrhythmics (HR 0.59, 95% CI 0.40-0.87; P=0.008). Adding LASEC to the CHADS-VASc score modestly improved predictive accuracy and risk classification, with a C index of 0.71 vs. 0.69 (P=0.004).
In this retrospective monocentric study, the presence of moderate/severe LASEC was an independent predictor of stroke/death at 5-year follow-up in patients with NVAF. The inclusion of LASEC in stroke risk scores could modestly improve risk stratification.
In this retrospective monocentric study, the presence of moderate/severe LASEC was an independent predictor of stroke/death at 5-year follow-up in patients with NVAF. The inclusion of LASEC in stroke risk scores could modestly improve risk stratification.